Rationale and objectivesThe off-label use of flow diverters (FDs) has broadened to include treating aneurysms in posterior circulation (PC). A novel flow diverter, the Tubridge flow diverter (TFD), has been created in China specifically for treating PC aneurysms. However, studies comparing between pipeline embolization device (PED) and TFD are rare. Thus, our study aimed to explore the effectiveness of PED and TFD in the treatment of PC aneurysms using a propensity score matched cohort design.MethodsRetrospective data collection was conducted on patients who underwent treatment with either PED or TFD over the period from 2015 through 2020. Propensity score matching (PSM) was employed to calibrate for patient age; history of ischemic stroke; aneurysm size; morphology; location and neck; number of FDs; parent vessel diameter; and the employment of assisted coiling and balloon techniques. Data on previously ruptured aneurysms was not included in the analysis. A comparison was conducted between the two devices to assess perioperative complications, aneurysm occlusion rates, and functional outcomes.ResultsA total of 252 PC aneurysms were treated in 248 patients. Clinical and imaging follow-ups were lost in 26 and 47 patients, respectively. Major perioperative complications occurred in 7.5% of the cases, with favorable clinical outcomes in 91.0% and complete occlusion in 79.1%. Eighty-two (32.5%) aneurysms were treated with TFD, while 170 (67.5%) aneurysms were treated with PED. PSM was used to account for these significant variations, producing 82 matched pairs of unruptured aneurysms treated with PED or TFD. In terms of functional and angiographic outcomes, no significant differences were found between PED and TFD (functional outcome, p = 0.594 and angiographic outcome, p = 0.415). However, more perioperative major complications were found in patients treated with TFD (p = 0.005) compared with those receiving PED.ConclusionThe comparative study of PED and TFD in the treatment of PC aneurysms resulted in positive clinical results and sustained occlusion rates, with acceptable perioperative complications. However, higher quality studies are needed to enhance our understanding of the use of FDs for treating of PC aneurysms.
With the boom of China's innovative pharmaceutical industry, licensing-in model has gradually become an important research and development model for innovative pharmaceutical companies. The in-licensed drugs at different stages need different research and development (R&D) strategy in China. The pharmaceutical companies take the responsibility to comprehensively collate the oversea clinical data and conduct a detailed analysis of clinical pharmacology, safety, efficacy and ethnic sensitivity. Clinical R&D strategy should be made based on the results of the above data and analysis. We encourage high-quality drugs which fill unmet clinical needs licensed in, and as early as possible, so as to conduct multi-regional clinical trials (MRCTs). The clinical R&D strategy in China is particularly important for the drug's approval. Guidelines published by the National Medical Products Administration (NMPA) and clinical associations should be followed. Communications about clinical R&D strategy with Center of Drug Evaluation (CDE) are encouraged. .【中文题目：境外授权许可引进抗肿瘤新药临床研发策略的审评考虑】 【中文摘要：随着我国创新药产业的蓬勃发展，授权许可引进逐渐成为创新药企的重要研发模式。不同研发阶段引进的药物，在中国的研发策略有所不同。企业需全面整理药物已产生的境外临床数据，对临床药理学、安全性、有效性和种族敏感性进行详细的分析。应基于上述数据和分析的结果制定合理的临床研发策略。我们鼓励引进中国境内真正未满足临床需求的优质药物，尽可能在研发的早期阶段引进，以实现国内外的同步研发。新药引进后的临床研发策略对于药物能否顺利上市尤为重要，企业应遵循国家药品监督管理局已发布的指导原则和相应的临床指南进行临床试验设计，积极与监管部门进行沟通。 】 【中文关键词：授权许可；抗肿瘤新药；研发策略；桥接研究】.
According to the relevant complete mRNA sequence of α-tubulin gene of Camellia sinensis (accession NO. DQ340766), the coding region of α-tubulin gene was amplified using RT-PCR method, and its products were expressed in Escherichia coli using the pET-32a(+) vector. The fusion protein was expressed in the form of inclusion body when induced with isopropyl-D-thiogalatopyranoside (IPTG), then was purified to immunize the rabbit to produce the polyclonal antibody against α-tubulin. The specificity of the antibody was confirmed by Western blot analysis. The results of Western blot revealed well specificity of the antibody against α-tubulin in Camellia sinensis plant.
Hemodynamic factors are believed to be closely related to IA growth. However, the underlying pathophysiological mechanism that induces the growth sequence in tandem intracranial aneurysms (IAs) remains unclear.This study involved five patients with tandem IAs. Aneurysm models were reconstructed based on image datasets. A novel vascular restoration algorithm was proposed to generate the hypothetical geometry of the healthy parent vessel before each IA formation in the concatenated structure. Detailed hemodynamic patterns and morphological features were revealed under various growth sequences of tandem IAs to investigate the flow-driven mechanism of IA growth. Potential hemodynamic indicators of IA formation were proposed.The patient cases were divided into two groups based on the size difference of tandem IAs. In the group with a similar size of tandem IAs, the position of the vortex core was associated with the site of the secondary aneurysm, while in the group with a significant size difference of the IAs, the position with the maximum curvature of the parent vessel plays a significant role in aneurysm formation.This study preliminarily revealed key hemodynamic and morphological indicators that determine the formation of tandem IAs. The proposed vascular restoration algorithm that provided the pre-aneurysm vasculature might be useful in investigating the flow-driven mechanism of IA growth, thus contributing to the risk evaluation of secondary aneurysm formation.
OBJECTIVE The authors undertook an evaluation of periprocedural cerebrovascular complications and 30-day outcomes of endovascular treatment for intracranial vertebral artery dissecting aneurysms (IVADAs) and assessed the relevant risk factors. METHODS The authors included a series of 195 patients who had undergone endovascular treatment for 198 IVADAs. Clinical data, morphological characteristics, treatment details, and periprocedural cerebrovascular complications including intraprocedural rupture, intraprocedural thrombosis, intracranial hemorrhage (ICH), transient ischemic attack (TIA), and ischemic stroke (IS) were recorded. After evaluation of the 30-day modified Rankin Scale (mRS) scores, the authors applied univariate and multivariate logistic regression analyses to identify the risk factors for complications and 30-day unfavorable clinical outcomes. RESULTS There were no intraprocedural ruptures, but the authors recorded intraprocedural thrombosis (n = 5), ICH (n = 3), TIA (n = 1), and IS (n = 13), comprising an 11.1% (22/198) complication rate. Multivariate logistic regression analysis indicated that hyperlipidemia (odds ratio [OR] 3.17, 95% confidence interval [CI] 1.20–8.41, p = 0.020), IS history (OR 5.55, 95% CI 1.46–21.01, p = 0.012), and subarachnoid hemorrhage (SAH) (OR 4.48, 95% CI 1.52–13.20, p = 0.007) were risk factors for overall complications, whereas aneurysmal height (OR 0.77, 95% CI 0.61–0.98, p = 0.032) was a protective factor. SAH (OR 6.44, 95% CI 1.54–26.89, p = 0.011) and preprocedural mRS score > 2 (OR 5.07, 95% CI 1.01–25.59, p = 0.049) were independent risk factors for perforator occlusion stroke. Periprocedural cerebrovascular complications (OR 32.09, 95% CI 3.00–343.94, p = 0.004) and preprocedural mRS score > 2 (OR 319.92, 95% CI 30.28–3379.98, p < 0.001) were independent risk factors for 30-day unfavorable clinical outcomes. CONCLUSIONS Hyperlipidemia, IS history, and SAH were independent predictors for overall periprocedural cerebrovascular complications of endovascular treatment for IVADAs, but aneurysmal height was an independent protective factor. SAH and preprocedural mRS score > 2 were independent risk factors for perforator occlusion stroke. Preprocedural mRS score > 2 and periprocedural complications were independent risk factors for 30-day unfavorable clinical outcomes.
Background Flow diverter devices (FDs) are increasingly used for treating unruptured intracranial aneurysms (UIAs), but limited studies compared different FDs. Objective To conduct a propensity score matched analysis comparing the Pipeline embolization device (PED) and Tubridge embolization device (TED) for UIAs. Methods Patients with UIAs treated with either PED or TED between July 2016 and July 2022 were included. Propensity score matching was performed to adjust for age, sex, comorbidities, smoking, drinking, aneurysm size, morphology, neck, location, parent artery diameter, adjunctive coiling, and angiographic follow-up duration. Perioperative complications and clinical and angiographic outcomes were compared after matching. Results 735 patients treated by PED and 290 patients treated by TED were enrolled. Compared with the PED group, patients in the TED group had a greater number of women and patients with ischemia, a smaller proportion of vertebrobasilar and non-saccular aneurysms, a smaller size and neck, and fewer adjunctive coils and overlapping stents, but a larger parent artery diameter and lumen disparities. After adjusting for these differences, 275 pairs were matched. No differences were found in perioperative complications (4.4% vs 2.5%, P=0.350), in-stent stenosis (16.0% vs 15.6%, P>0.999), or favorable prognosis (98.9% vs 98.5%, P>0.999). However, PED showed a trend towards better complete occlusion over a median 8-month angiographic follow-up (81.8% vs 75.3%, P=0.077). Conclusion Compared with PED, TED provides a comparable rate of perioperative and short-term outcomes. Nevertheless, a better occlusion status in the PED group needs to be further verified over a longer follow-up period.
Missing Not at Random (MNAR) and nonnormal data are challenging to handle. Traditional missing data analytical techniques such as full information maximum likelihood estimation (FIML) may fail with nonnormal data as they are built on normal distribution assumptions. Two-Stage Robust Estimation (TSRE) does manage nonnormal data, but both FIML and TSRE are less explored in longitudinal studies under MNAR conditions with nonnormal distributions. Unlike traditional statistical approaches, machine learning approaches do not require distributional assumptions about the data. More importantly, they have shown promise for MNAR data; however, their application in longitudinal studies, addressing both Missing at Random (MAR) and MNAR scenarios, is also underexplored. This study utilizes Monte Carlo simulations to assess and compare the effectiveness of six analytical techniques for missing data within the growth curve modeling framework. These techniques include traditional approaches like FIML and TSRE, machine learning approaches by single imputation (K-Nearest Neighbors and missForest), and machine learning approaches by multiple imputation (micecart and miceForest). We investigate the influence of sample size, missing data rate, missing data mechanism, and data distribution on the accuracy and efficiency of model estimation. Our findings indicate that FIML is most effective for MNAR data among the tested approaches. TSRE excels in handling MAR data, while missForest is only advantageous in limited conditions with a combination of very skewed distributions, very large sample sizes (e.g., n larger than 1000), and low missing data rates.
We aimed to develop and validate a morphology-based radiomics signature nomogram for assessing the risk of intracranial aneurysm (IA) rupture. A total of 254 aneurysms in 105 patients with subarachnoid hemorrhage and multiple intracranial aneurysms from three centers were retrospectively reviewed and randomly divided into the derivation and validation cohorts. Radiomics morphological features were automatically extracted from digital subtraction angiography and selected by the least absolute shrinkage and selection operator algorithm to develop a radiomics signature. A radiomics signature-based nomogram was developed by incorporating the signature and traditional morphological features. The performance of calibration, discrimination, and clinical usefulness of the nomogram was assessed. Ten radiomics morphological features were selected to build the radiomics signature model, which showed better discrimination with an area under the curve (AUC) equal to 0.814 and 0.835 in the derivation and validation cohorts compared with 0.747 and 0.666 in the traditional model, which only include traditional morphological features. When radiomics signature and traditional morphological features were combined, the AUC increased to 0.842 and 0.849 in the derivation and validation cohorts, thus showing better performance in assessing aneurysm rupture risk. This novel model could be useful for decision-making and risk stratification for patients with IAs.
Clinically, metabolic syndrome (MetS) is associated with the formation and relapse of kidney stones diseases (KSD). In the general population, dietary selenium can reduce renal damage by reducing oxidative stress and other physiological pathways. Less is known, however, about the association between dietary selenium and KSD in patients with MetS.
To screen the protein interacting with apoptin from human leucocyte cDNA library by using yeast two-hybrid system, four clones interacting with apoptin were identified. One of them was homologous with Nmi (N-Myc interaction protein). Cell co-immunoprecipitation showed that apoptin could bind to Nmi in mammalian cells. Apoptin mutants T1, T2 and T3 lacked the C-terminal 11 AA,33-46 AA and both,respectively. Apoptin mutants T2 and T3 failed to interact with Nmi, suggesting that its 33-46 AA was pivotal for the interaction. Apoptin mutant T1 still interacted with Nmi, suggesting that its C-terminal 11 AA was not essential for the interaction.
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